Bacterial antibiotic resistance has become one of the most serious threats to modern health care. Infections caused by resistant bacteria frequently result in longer hospital stays, higher mortality and increased cost of treatment. See, e.g., Cohen, Science 1992, 257:1051-1055. The spread of antibiotic resistance has been referred to as a pandemic and that a solution to the growing public health threat will require an interdisciplinary approach. See, e.g., Anderson, Nat. Med. 1999, 5: 147-149. See also Bush et al., Nat. Rev. Microbiol. 2011, 9: 894-896; Levy and Marshall, Nat. Med. 2004, 10: S122-S129; Livermore, Clin. Infect. Dis. 2003, 36: S11-S23; and Roberts et al., Clin. Infect. Dis. 2009, 49: 1175-1184.
The present crisis has prompted various efforts to elucidate the mechanisms responsible for bacterial resistance. The widespread use of penicillins and cephalosporins has resulted in the emergence of β-lactamases, a family of bacterial enzymes that catalyze the hydrolysis of the β-lactam ring common to numerous presently used antibiotics. See, Coulton et al., Prog. Med. Chem. 1994, 31: 297-349. This family of bacterial β-lactamases is further divided into four sub-families: A, C, and D which have a serine at the active site that catalyzes the hydrolysis of β-lactam antibiotics and a B family β-lactamases which are zinc metalloenzymes. Resistance mediated by β-lactamases is a critical aspect at the core of the development of bacterial antibiotic resistance. See, Dudley, Pharmacotherapy 1995, 15: 9S-14S. Clavulanic acid, which is a metabolite of Streptomyces clavuligerus, and two semi-synthetic inhibitors, sulbactam and tazobactam, are currently available semi-synthetic or natural product β-lactamase inhibitors. Synthetic β-lactamase inhibitors have also been described. See, U.S. Pat. Nos. 5,698,577; 5,510,343; 6,472,406; Hubschwerlen et al., J. Med. Chem. 1998, 41: 3961; and Livermore et al., J. Med. Chem. 1997, 40:335-343. Poole, Cell. Mol. Life Sci. 2004, 61: 2200-2223 provides a review of the resistance of bacterial pathogens to β-lactam antibiotics and approaches for overcoming resistance. For a review of inhibitors of metallo β-lactamases, see Fast and Sutton, Biochim. Biophys. Acta—Proteins and Proteomics 2013, 1834(8):1648-1659.
U.S. Patent Application Publication No. US 2003/0199541 A1 discloses certain azabicyclic compounds including certain 7-oxo-6-diazabicyclic[3.2.1]octane-2-carboxamides and their use as anti-bacterial agents. U.S. Patent Application Publication No. US 2004/0157826 A1 discloses heterobicyclic compounds including certain diazepine carboxamide and diazepine carboxylate derivatives and their use as anti-bacterials and β-lactamase inhibitors. International Patent Application Publication No. WO 2008/039420 A2 discloses 7-oxo-2,6-diazabicyclo[3.2.0]heptane-6-sulfooxy-2-carboxamides and their use as β-lactamase inhibitors.
Zheng et al., in PLOS One 2013, 8(5), e62955, discloses substituted 2,5-bis-tetrazolylmethyl-thiophenes and their use as β-lactamase inhibitors. Chinese Patent Application Publication No. CN103130686 A discloses N,N′-diaryl-ureas and their use as inhibitors of metallo β-lactamases. Chinese Patent Application Publication No. CN103191091 A discloses substituted arylsulfonamides and their use as inhibitors of metallo β-lactamases.
U.S. Pat. Nos. 4,786,311; 4,746,353; 4,838,925; European Patent Application Publication Nos. EP204513A2, EP244166A2, and Chinese Patent Application Publication No. CN1095549A disclose substituted 2-(1H-tetrazol-5-yl)benzenesulfonamides and their use as herbicides.
Substituted β-tetrazolyl-propionamides and their use as agents for the treatment of Alzheimer's disease have been described. See Yang et al., Tet. Lett. 2004, 45: 111-112 and U.S. Patent Application Publication No. US 2004/0082568 A1.